1. Field of the Invention
This invention relates to an integrated-optical chemical and/or biochemical sensor and to a method for integrated-optically sensing a chemical and/or biochemical substance.
2. Description of Related Art
Many present and upcoming applications of biochemical microsystems, especially for application areas such as medical, food and environmental, require the detection of several analytes being simultaneously present in a liquid.
One well-known and advantageous type of detection is optical. Among optical sensors, an important class are integrated optical (IO) sensors comprising a chip with a waveguide and sensing biolayers. Examples of IO biosensors are given in WO 92/19976 (CSEM); R.E. Kunz, xe2x80x9cTotally Integrated Optical Measuring Sensors,xe2x80x9d Proc. SPIE, Vol. 1587, 98-113 (1992); WO 96/35940 (Ciba-Geigy).
Different sensing principles are being used. This invention deals with a subclass of sensors based on amplitude effects, i.e. those where the amplitudes of light waves (guided or/and freely propagating) are changed by the effect to be measured. Examples are luminescence (e.g. fluorescence, (electro-)chemo-luminescence), absorption or scattering (e.g. elastic and Raman).
The state-of-the-art procedure is to use two grating couplers (one input and a separate output). The publication EP-A-1,031,828 concerns a referencing scheme, which is also applicable for the new schemes disclosed here.
Drawbacks and problems of the state-of-the-art solutions are that they require too much of chip area, leading to very big chips and also to a small ratio between active and passive area. It also needs too much of (bio-)chemical area, since this is not efficiently used. Another problem with presently known array detection schemes is that the efficiency of on-chip referencing is limited by the large distance between sensing and referencing pads.
Sensing (signal) and referencing pads are both denoted by the term xe2x80x9cmeasuring padxe2x80x9d in this document.
This invention aims at removing the drawbacks of the state-of-the art solutions for achieving amplitude-based high-density array sensors by reducing the area required for performing the sensing task, especially by reducing the area required by a single measuring pad in an array, and by increasing the ratio between active and passive chip area.
It is a further object of the invention to provide an IO sensor with:
more efficient on-chip referencing
chip and system miniaturization, i.e., more sensing pads per chip area (in the case of a two-dimensional sensor) or per volume (in the case of a three-dimensional sensor)
less chemicals needed for chip biocoating
less analyte volume needed due to reduced chip area for performing same task.
To take full advantage for practical applications, the following constraints shall be taken into account:
the sensitivity is maintained or increased with respect to the conventional solutions; and
the dynamic range is maintained or increased with respect to the conventional solutions.
This goal is achieved by realizing one or a combination of the following inventive measures:
increasing the functionality of the measuring pads;
adapting the measuring pad geometry to the sensing principle, to the overall chip geometry, and to the application;
enhancing the efficiency of light collection (in general: xe2x80x9coptical transfer processesxe2x80x9d);
reducing the crosstalk between individual measuring pads by more efficient and more localized xe2x80x9clight extractionxe2x80x9d and/or by means of the geometry of the measuring pads.
The integrated-optical chemical and/or biochemical sensor according to the invention comprises
a resonant waveguide structure;
means for at least temporarily depositing a chemical and/or biochemical substance to be sensed on a surface of the resonant waveguide structure;
means for irradiating the substance with electromagnetic radiation, making use of a first set of degrees of freedom;
means for coupling out electromagnetic radiation from the resonant waveguide structure, making use of a second set of degrees of freedom which differs from the first set of degrees of freedom in at least one degree of freedom; and
means for detecting electromagnetic radiation exiting from the resonant waveguide structure.
The irradiating means and/or the outcoupling means preferably comprise grating structures. The first and second set of degrees of freedom preferably comprises the diffraction order, the polarization, the guided-mode order, the grating vector and/or the planes of incidence and emergence.
The method according to the invention for integrated-optically sensing a chemical and/or biochemical substance using a resonant waveguide structure comprises the steps of
irradiating the substance with first electromagnetic radiation, thereby using a first set of degrees of freedom;
causing the substance to interact with the first electromagnetic radiation in such a way that it emits second electromagnetic radiation which differs in at least one parameter from the first electromagnetic radiation;
causing the second electromagnetic radiation to excite a resonant electromagnetic field in the resonant waveguide structure;
coupling electromagnetic radiation out from the resonant waveguide structure, thereby using a second set of degrees of freedom which differs from the first set of degrees of freedom in at least one degree of freedom; and
detecting electromagnetic radiation exiting from the resonant waveguide structure.
The interaction of the substance with the first electromagnetic radiation preferably comprises luminescence, scattering, absorption, chemiluminescence and/or electrochemi-luminescence. The first and second set of degrees of freedom preferably comprises the diffraction order, the polarization, the guided-mode order, the grating vector and/or the planes of incidence and emergence.
Hence, a much higher density of sensing pads results for single-chip sensors, leading to several advantages as is described below. An important improvement is achieved for on-chip referencing, which is eased due to the smaller distance between measuring pads, and because multiple referencing pads can be used per sensing pad, e.g. one on top and one below or left and right or distributed around etc. This is especially important for sensors with very high sensitivities, since they are more affected by unspecific effects such as temperature and signal drift due to chemical and physical fluctuations.
The sensor according to the invention can be combined with known integrated-optical sensors based on other principles such as refractometry, for example using an integrated-optical light pointer (see, e.g., R.E. Kunz, xe2x80x9cMiniature integrated optical modules for chemical and biochemical sensingxe2x80x9d, Sensors and Actuators B 38-39 (1997) 13-28).